The Center for Psychiatric Neuroscience (CPN) at The University of Mississippi Medical Center (UMMC), initiated four years ago through a COBRE grant, has developed a multidisciplinary team committed to understanding the etiology of depression. The center now has the potential to develop and sustain an innovative and independently funded research center focused on depression. Faculty in the Center and its academic home, the Department of Psychiatry &Human Behavior, have already reported groundbreaking observations on the roles of neurons, glia, cerebral vasculature, aging, gender, serotonin and glutamate in the etiology of depression. COBRE-supported investigators have increased their competitiveness by attracting extramural funds and publishing in leading journals of neuroscience. The Center will continue to provide an excellent environment for junior and mid-level investigators by working in close collaboration with leading national centers and scientists studying depression to carry out the proposed projects that build on these novel insights into the pathophysiology of depression. To achieve the goal of establishing an innovative and multidisciplinary Center focused on depression, the following Specific Aims are proposed: Aim 1 is to enhance the competitive independent research funding of four investigators, as detailed in research proposals. In addition, leading external and internal scientists in depression will continue to mentor all Center faculty in basic and clinical neuroscience. Aim 2 is to continue the expansion of research resources for the development of innovative depression related projects. Core facilities to accomplish this will include: a) a postmortem human brain collection, b) an animal brain collection focused on behavioral studies related to depression and its treatment, c) imaging facilities for studying quantitative brain biology at the cellular level, and (d) resources for the implementation of molecular biological techniques. Aim 3 is to continue faculty development and growth of new neuroscience investigators through training in cutting-edge technologies and to promote research opportunities in neuroscience for undergraduate and graduate students being mentored by Center faculty. Aim 4 is to sponsor a competitive small grant program that advances research in depression related to the themes outlined in the proposal. The focus on depression, projects examining integrated models, an outstanding Center faculty, training opportunities, a small grant program and generous support by the UMMC administration will ensure the continued growth of a research center that is innovative and multidisciplinary, and moving strongly toward independent funding, and development of a core of senior and new neuroscience faculty.